Increased cell-intrinsic excitability induces synaptic changes in new neurons in the adult dentate gyrus that require Npas4.

Electrical activity regulates the manner in which neurons mature and form connections to each other. However, it remains unclear whether increased single-cell activity is sufficient to alter the development of synaptic connectivity of that neuron or whether a global increase in circuit activity is necessary. To address this question, we genetically increased neuronal excitability of in vivo individual adult-born neurons in the mouse dentate gyrus via expression of a voltage-gated bacterial sodium channel. We observed that increasing the excitability of new neurons in an otherwise unperturbed circuit leads to changes in both their input and axonal synapses. Furthermore, the activity-dependent transcription factor Npas4 is necessary for the changes in the input synapses of these neurons, but it is not involved in changes to their axonal synapses. Our results reveal that an increase in cell-intrinsic activity during maturation is sufficient to alter the synaptic connectivity of a neuron with the hippocampal circuit and that Npas4 is required for activity-dependent changes in input synapses.

Olfactory coding: when smells collide.

Brain responses can significantly outlast sensory stimuli leading to potential ambiguity when responses overlap. Recent studies of locust olfaction found that the responses of individual second order projection neurons depend markedly on the previous few seconds' stimulus history; the population response, however, still conveys information about both temporal structure and odour identity.

Olfactory response termination involves Ca2+-ATPase in vertebrate olfactory receptor neuron cilia.

In vertebrate olfactory receptor neurons (ORNs), odorant-induced activation of the transduction cascade culminates in production of cyclic AMP, which opens cyclic nucleotide-gated channels in the ciliary membrane enabling Ca(2+) influx. The ensuing elevation of the intraciliary Ca(2+) concentration opens Ca(2+)-activated Cl(-) channels, which mediate an excitatory Cl(-) efflux from the cilia. In order for the response to terminate, the Cl(-) channel must close, which requires that the intraciliary Ca(2+) concentration return to basal levels. Hitherto, the extrusion of Ca(2+) from the cilia has been thought to depend principally on a Na(+)-Ca(2+) exchanger. In this study, we show using simultaneous suction pipette recording and Ca(2+)-sensitive dye fluorescence measurements that in fire salamander ORNs, withdrawal of external Na(+) from the solution bathing the cilia, which incapacitates Na(+)-Ca(2+)exchange, has only a modest effect on the recovery of the electrical response and the accompanying decay of intraciliary Ca(2+) concentration. In contrast, exposure of the cilia to vanadate or carboxyeosin, a manipulation designed to block Ca(2+)-ATPase, has a substantial effect on response recovery kinetics. Therefore, we conclude that Ca(2+)-ATPase contributes to Ca(2+) extrusion in ORNs, and that Na(+)-Ca(2+)exchange makes only a modest contribution to Ca(2+) homeostasis in this species.

The effect of external sodium concentration on sodium-calcium exchange in frog olfactory receptor cells.

During the response of vertebrate olfactory receptor cells to stimulation, Ca(2+) enters the cilia via cyclic nucleotide-gated channels and is extruded by Na(+)-Ca(2+) exchange. The rise in Ca(2+) concentration opens a Ca(2+)-activated Cl(-) conductance which carries most of the inward receptor current. The dependence of Ca(2+) extrusion upon external Na(+) concentration was studied by using the falling phase of the Ca(2+)-activated Cl(-) current following a brief exposure to the phosphodiesterase inhibitor IBMX to monitor indirectly the decay in intraciliary Ca(2+) concentration. External Na(+) concentration was reduced by partial substitution with guanidinium, an ion which permeates the cyclic nucleotide-gated channel but does not support Na(+)-Ca(2+) exchange. The time constant describing the decay in current following IBMX stimulation was surprisingly little affected by substitution of external Na(+), being substantially retarded only when its concentration was reduced to a third or less of its normal value in Ringer solution. When the cilia were returned to Ringer solution after a period in reduced-Na(+) solution, the time constant for the final decay of current was similar to that seen when returning immediately to IBMX-free Ringer solution. This observation suggests that Ca(2+) extrusion via Na(+)-Ca(2+) exchange dominates the falling phase of the response to IBMX, which can therefore be used to assess exchanger activity. Rate constants derived from the time constants for current decay at different external Na(+) concentrations could be fitted by the Hill equation with a K(d) of 54 +/- 4 mm and Hill coefficient of 3.7 +/- 0.4. The cooperativity of the dependence upon external Na(+) concentration indicates that at least three Na(+) ions enter for each exchanger cycle, while the high affinity for external Na(+) contrasts with the photoreceptor and cardiac exchangers. The functional importance of this observation is that the relative insensitivity of the Na(+)-Ca(2+) exchanger to external Na(+) concentration allows normal response termination even following partial dilution or concentration of the olfactory mucus.